The neurotransmitter ATP acts on receptors found on a variety of cell types. Physiological data suggest that both ligand gated P2X and G- protein coupled P2Y ATP receptors are found on cells in the guinea pig organ of Corti. It has been proposed that activation by ATP of inotropic (P2X) receptors on outer hair cells (OHCs) of the organ of Corti leads to depolarization and an increase in intracellular Ca2+. The ATP-induced response of Deiters cells may modify the voltage- induced OHC motility. OHC motility appears to be the basis for the cochlear amplifier which transmits low intensity stimuli to the inner hair cells. The goal of the proposed research is to test the hypothesis that endogenous ATP modulates the function of the cochlear amplifier (active process) in the organ of Corti. This goal will be accomplished by isolation and sequencing of P2X receptor types found in an organ of Corti library, identification by in situ hybridization of the specific organ of Corti cell types which contain P2X mRNAs, and determination of the in vivo effect of reduction of P2X receptors in the organ of Corti via application of antisense technology.